NLF-1 delivers a sodium leak channel to regulate neuronal excitability and modulate rhythmic locomotion

Neuron. 2013 Mar 20;77(6):1069-82. doi: 10.1016/j.neuron.2013.01.018.

Abstract

A cation channel NCA/UNC-79/UNC-80 affects neuronal activity. We report here the identification of a conserved endoplasmic reticulum protein NLF-1 (NCA localization factor-1) that regulates neuronal excitability and locomotion through the NCA channel. In C. elegans, the loss of either NLF-1 or NCA leads to a reduced sodium leak current, and a hyperpolarized resting membrane potential in premotor interneurons. This results in a decreased premotor interneuron activity that reduces the initiation and sustainability of rhythmic locomotion. NLF-1 promotes axonal localization of all NCA reporters. Its mouse homolog mNLF-1 functionally substitutes for NLF-1 in C. elegans, interacts with the mammalian sodium leak channel NALCN in vitro, and potentiates sodium leak currents in primary cortical neuron cultures. Taken together, an ER protein NLF-1 delivers a sodium leak channel to maintain neuronal excitability and potentiates a premotor interneuron network critical for C. elegans rhythmic locomotion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Caenorhabditis elegans Proteins / physiology
  • Cells, Cultured
  • Endoplasmic Reticulum / metabolism
  • Gene Knockdown Techniques / methods
  • Locomotion / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neurons / metabolism*
  • Nuclear Proteins
  • Periodicity*
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Sodium Channels / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology

Substances

  • C2CD4A protein, human
  • Caenorhabditis elegans Proteins
  • NALCN protein, human
  • Nuclear Proteins
  • Sodium Channels
  • Transcription Factors

Associated data

  • GENBANK/KC514050